Therapeutic Innovation & Regulatory Science

Có một nhu cầu ngày càng tăng về việc sử dụng dữ liệu bên ngoài, chẳng hạn như dữ liệu nghiên cứu lịch sử và dữ liệu đăng ký bệnh nhân, để bổ sung cho nhóm đối chiếu trong một thử nghiệm ngẫu nhiên đối chiếu. Mặc dù thiết kế nghiên cứu như vậy có thể giảm thời gian và chi phí, nhưng cách duy trì tính hợp lệ và tính toàn vẹn của nghiên cứu là một thách thức thống kê chính cần được giải quyết một cách cẩn thận. Chúng tôi thảo luận về quy trình chất lượng thiết kế nghiên cứu để nâng cao tính hợp lệ và toàn vẹn của nghiên cứu khi sử dụng phương pháp này. Quy trình chất lượng đã được thảo luận được tùy chỉnh cho nghiên cứu xác nhận sử dụng thiết kế 2 giai đoạn với sự nhấn mạnh vào quá trình tương tác giữa các bên liên quan. Trong một ví dụ, quy trình chất lượng bao gồm việc đánh giá 2 bước về sự tương đồng trong các đặc điểm của bệnh nhân giữa nghiên cứu hiện tại và nguồn dữ liệu bên ngoài, cũng như giữa nhóm điều trị và nhóm đối chiếu được tăng cường.

Editor’s Note: In this Meeting Report, Tetsuomi Takano provides an excellent summary of 2 related tutorial sessions held at the DIA 6th Annual Conference in Japan for Asian New Drug Development (KFC Hall, Tokyo, Japan, April 27, 2012). The sessions focused on best practices for development regulatory affairs and clinical development related to multiregional clinical trials (MRCTs) in China, Korea and Taiwan. I am grateful to Mr Takano for this contribution to the journal, and I am sure readers will find it both interesting and educational. J. Rick Turner, Outgoing Editor-in-Chief

Clinical trials should be part of routine health care. There is a common perception that enrolling patients into clinical trials results in additional costs. We conducted a retrospective cost analysis to compare medical costs attributable to participation in cancer treatment trials versus standard of care in a single Spanish institution. Patients recruited into cancer clinical trials between 2014 and 2016 were selected. Each research protocol was reviewed to identify trial-associated medical procedures and costs, as well as the equivalent care had the patient not been entered in the trial. Treatment cost difference was the difference between the cost of the clinical trial and that of the standard of care. A total of 68 adult patients were treated in 20 different clinical trials. The overall cost treatment of the patients included in the trials was 79% lower in comparison to the standard of care. However, the load of medical procedures was 32% higher. The average treatment cost per patient and protocol ranged from an excess of €8193 to a saving of €59,770. There is a wide range of difference in treatment costs for cancer clinical trial participants versus standard of care. Commercial trial protocols were associated with larger savings compared with the noncommercial ones, even though these may involve excess treatment costs. Overall, clinical trials provide not only the best context for progress of clinical research and health care but also creates opportunities for reducing cancer care costs.

The urgency and impact of the ongoing COVID-19 pandemic are changing global drug development and regulatory processes. The need for speed to understand the virus and develop new vaccines, medicines, and therapies for patients has provided unprecedented learning opportunities and revealed how the pharmaceutical industry can improve upon traditional processes. To stay competitive while remaining compliant with agency regulations and guidance, companies need to implement new process/tools that allow for more flexible work models, consider expanding the use of decentralized/hybrid trials, and capitalize on the use of real-world evidence (RWE) and cloud-based data systems. In addition, regulatory agencies should retain the agility exhibited during current reviews of potential new therapies, applying this momentum to other areas of unmet medical need. Further, agencies should consider a globally acceptable application platform. This article, by the Pharmaceuticals’ Head of Regulatory Affairs at Bayer AG, examines how impacts of the COVID-19 crisis will continue beyond the pandemic period to the benefit of patients, drug developers, regulators, clinicians, and caregivers.

TransCelerate BioPharma Inc developed a methodology based on the notion that shifting monitoring processes from an excessive concentration on source data verification to comprehensive risk-driven monitoring will increase efficiencies and enhance patient safety and data integrity while maintaining adherence to good clinical practice regulations. This philosophical shift in monitoring processes employs the addition of centralized and off-site mechanisms to monitor important trial parameters holistically, and it uses adaptive on-site monitoring to further support site processes, subject safety, and data quality. The main tenet is to use available data to monitor, assess, and mitigate the overall risk associated with clinical trials. Having the right technology is critical to collect and aggregate data, provide analytical capabilities, and track issues to demonstrate that a thorough quality management framework is in place. This paper lays out the high-level considerations when designing and building an integrated technology solution that will aid in scaling the methodology across an organization’s portfolio.

The traditional economic model for drug development by leading pharmaceutical companies in the developed world has yielded diminishing returns in recent years, with large pharmaceutical companies relying less on research and development and more on cost cutting and obtaining promising drug candidates through mergers and acquisitions. Concurrently, drug companies in emerging markets have flourished under a different economic model characterized by public-private partnerships, government subsidy, and profitable marketing of generic drugs. These companies are now focusing on research and development of innovative drug candidates, including drugs that treat neglected diseases such as tuberculosis and hepatitis. However, drug companies in developing countries may lack the expertise of leading drug companies to navigate the complicated regulatory system. This article highlights an opportunity for companies with drug development expertise to partner with companies in the developing world with innovative pipeline drugs.

To evaluate the quality of the decision-making processes of pharmaceutical companies during medicines development for evidence generation to support reimbursement of new medicines and the appraisal recommendation decision-making process by health technology assessment (HTA) agencies. Two questionnaires were developed and subsequently piloted for the purpose of content validation. These were sent to 24 pharmaceutical companies and 16 HTA agencies. Responses were obtained from 11 companies and 11 HTA agencies. Some similarities were identified between the decision-making processes of companies and agencies, such as the use of committees, having a primarily mixed (qualitative/quantitative) internal decisionmaking system, as well as the lack of systematic assessments of quality decision making and the relatively infrequent use of formal decision-making frameworks. Nevertheless, the results indicate differences as companies and agencies use diverse processes to arrive at the final decision either through consensus, majority vote, or an individual making the decision. The majority of companies and agencies believe that the quality of decision making can and should be measured. Moreover, organizations considered the occurrence of biases within their organization as pertinent. Finally, almost all the participants felt that there was room for improvement for their organization’s quality of decision making. These findings are consistent with a published study on regulatory processes and support the need for more consistent and predictable decision-making processes during the life cycle of medicines. This could be achieved through capacity building, systematically evaluating the quality of decision making, and encouraging utilization of formal decision-making frameworks within companies and agencies.

The Medical Information Department of a pharmaceutical manufacturer provides written scientific responses to unsolicited requests from healthcare providers for information on products that extends beyond the product labeling (off-label). These scientific response documents are non-promotional, evidence-based, and scientifically balanced, conforming with internal pharmaceutical manufacturer’s procedures and the Food and Drug Administration (FDA) Draft Guidance on Responding to Unsolicited Requests for Off-Label Information. Members of phactMI™ developed this proposal to offer best practices for content generation of scientific response documents. Scientific response documents review available literature to respond to an unsolicited request; therefore, they are similar in nature to systematic reviews. The sections and elements identified in this proposed best practice guidelines for scientific response documents are based on an adaptation of the sections and elements of systematic reviews. The sections of a scientific response document should include a restatement of the unsolicited request (title); a structured summary (abstract); approved indications, black box warnings, and background information when appropriate (introduction); the literature search information and study selection (methods); summation of data from clinical trials, meta-analysis, case reports, and/or real world evidence, as appropriate (results); treatment guidelines, if applicable and available (discussion); and references. Elements for each section should be included in a scientific response document as appropriate, as some elements are not necessary in some documents, based on the question. These elements were selected for inclusion to address any potential concerns of bias and transparency and reflect the intent that scientific response documents should be non-promotional, accurate, truthful, free of commercial bias, scientifically balanced, and evidence based.